Ankylosing Spondylitis: More Than Just the Spine

The eyes, skin, and bowel all can be affected.

Extra-articular disease manifestations that can have substantial impact on quality of life are common among patients with ankylosing spondylitis, a meta-analysis found.

Across published studies, the pooled prevalence of acute anterior uveitis among patients with this inflammatory spine disease was 25.8% (95% CI 24.1-27.6), according to Carmen Stolwijk, MD, of Maastricht University Medical Center in the Netherlands, and colleagues.

In addition, the pooled prevalence of psoriasis was 9.3% (95% CI 8.1-10.6), while the prevalence of inflammatory bowel disease was 6.8% (95% CI 6.1-7.7), the researchers reported in the January issue of Annals of the Rheumatic Diseases.

In the general population, the estimated prevalence of acute anterior uveitis is 0.2% to 1%, while the prevalence of psoriasis is 0.3% to 2.5% and that of inflammatory bowel disease is 0.01% to 0.5%, they noted.

In recent years there has been increasing interest in the extra-articular manifestations of ankylosing spondylitis and the related spondyloarthropathies, but accurate information on the prevalence and related factors has been lacking.

Therefore, Stolwijk and colleagues conducted a systematic literature review for studies published between 1984 and 2012, identifying 156 that met their inclusion criteria on symptoms beyond the spine.

"We hypothesized that the prevalences of all [extra-articular manifestations] would be associated with disease duration and with geographical area, the latter being associated with differences in distribution of HLA-B27 positivity," they noted.

HLA-B27 is a surface antigen in the major histocompatibility complex located on chromosome 6 that is strongly associated with the spondyloarthropathies.

A total of 143 studies that included 44,372 patients reported on the prevalence of acute anterior uveitis. In these studies, considerable heterogeneity was found (I2=94%). The prevalence was significantly associated with duration of disease, rising to 38.5% (95% CI 33.3-43.9) after 20 years from 17.4% (95% CI 14.3-21.3) at 10 years.

Significant differences in uveitis also were seen according to geographic area, with rates of 35.2% in North American patients with ankylosing spondylitis compared with 21.4% in Asia and 20.1% in Latin America.

In 56 studies that included 27,626 patients, the prevalence of psoriasis was reported and, once again, heterogeneity was substantial (I2=91%).

Geographic location was associated with prevalence, with rates of 10.9% in Europe, 4.2% in the Middle East, and 3.1% in Asia.

For inflammatory bowel disease, there were 69 studies with 32,341 patients, and considerable heterogeneity was present (I2=84.2%). Geographic location again was associated with different rates, being 9.6% in Latin America and 2.9% in Asia.

The researchers then conducted meta-regression analyses for each of the three extra-articular disease manifestations "to explore the methodological and clinical heterogeneity among the studies. Disease duration and geographical area were the most striking contributors to heterogeneity found," they explained.

For psoriasis, geographic area was significant, with lower estimates being seen for Asia (beta=-1.33, 95% CI minus 2.09-minus 0.57) and the Middle East (beta=-1.03, 95% CI minus 1.73-minus 0.32) versus Europe.

For inflammatory bowel disease, geographic location also was significant in this analysis, being lower in Asia (beta=-0.80, 95% CI minus 1.29-minus 0.32) than in Europe. The percentage of women included in the studies also was significant for inflammatory bowel disease (beta=0.02, 95% CI 0-0.03).

As to the finding that geographical location was a significant factor in the prevalence of extra-articular manifestations, the authors cautioned that not all of the variation was likely to relate to differences in rates of HLA-B27 positivity. The significant association remained after adjusting for HLA-B27, "suggesting that other (epi)genetic factors are likely to play a role."

Limitations of the study included the possibility of bias from confounding and missing information on factors such as disease duration in some studies.

The authors concluded, "The prevalence of [extra-articular manifestations] among patients with [ankylosing spondylitis] is clearly increased compared with the general population ... Awareness of [extra-articular manifestations] among clinicians is important in view of their role in the diagnostic process, for treatment choices, and for health-related quality of life."

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